A new mitochondrial point mutation in the transfer RNA(LYs) gene associated with progressive external ophthalmoplegia with impaired respiratory regulation

作者：Wolf Joachim^*; Obermaier Kusser Bert; Jacobs Martina; Milles Cornelia; Moerl Mario; von Pein Harald D; Grau Armin J; Bauer Matthias F

来源：Journal of the Neurological Sciences, 2012, 316(1-2): 108-111.

DOI：10.1016/j.jns.2012.01.013

• Progressive external ophthalmoplegia
• Mitochondrial disorders
• Mitochondrial tRNA
• Mitochondrial DNA mutation
• Respiratory insufficiency

We report a novel heteroplasmic point mutation G8299A in the gene for mitochondrial tRNA(LYs) in a patient with progressive external ophthalmoplegia complicated by recurrent respiratory insufficiency. Biochemical analysis of respiratory chain complexes in muscle homogenate showed a combined complex I and IV deficiency. The transition does not represent a known neutral polymorphism and affects a position in the tRNA acceptor stem which is conserved in primates, leading to a destabilization of this functionally important domain. In vitro analysis of an essential maturation step of the tRNA transcript indicates the probable pathogenicity of this mutation. We hypothesize that there is a causal relationship between the novel G8299A transition and progressive external ophthalmoplegia with recurrent respiratory failure due to a depressed respiratory drive.

• 出版日期2012-5-15